Protein Kinase C Inhibitors

Protein kinase C (PKC) are enzymes that add phosphate-groups to Serine/Threonine residues on a large variety of target proteins to regulate their activity in different signal transduction cascades affecting a multitude of cellular processes. PKC mediated phosphorylation is triggered by an increase in diacylglycerol (DAG) or calcium (Ca2+) concentration and the presence of a phospholipid like phosphatidylserine. In humans there are 15 known isoforms of PKC enzymes. One of the main characteristic hallmarks of PKC-signaling is long-term activation referring to the ability of these enzymes to remain in the "ON" mode long after the initial trigger has subsided. Phorbol-esters which are potent tumorigenic agents and in some instances, fatty acids, can substitute for DAG in activating PKCs and result in long-term potentiation. PKCs are curiously versatile enzymes in the sense that they can not only function as kinases but also as phosphatases and ATPases. They are involved in receptor desensitization, membrane structure remodeling and dynamics, transcriptional regulation, immune responses, cell growth and in learning and memory to name some of their most important physiological roles. Regulation of PKCs is a very finely-tuned process and any aberrations can result in diseases (cancer, diabetes, bipolar disorder, immune dysfunction as in HIV infections, cardiovascular disease, metabolic disturbances etc.) encompassing many organ systems and functions. Due to the differential levels of expression of PKCs in different cell types and the large number of PKC substrates in-vivo, specific inhibitors are sought to understand the function of each isoform and target proteins involved in different diseases. BioVision's product list includes an array of inhibitors that can target most of the prominent PKC isozymes.